Epstein-Barr virus has long been known to induce NFkB signaling through its latency associated membrane protein, LMP1. Recently our lab has challenged the dogma that NFkB signaling is constitutive at all times throughout infection by demonstrating that LMP1 protein and signaling do not accumulate to meaningful levels until around two weeks after infection. Transcriptional profiling of both EBV-infected cell lines and EBV-infected B blasts early after infection has revealed that transcription of the LMP1 gene increases 15-fold, the mRNA half-life increases 2-fold, and the total mRNA increases 50-fold compared to early times after infection. The LMP1 promoter is controlled by viral genes such as Epstein-Barr Nuclear Antigen (EBNA) 2 as well as EBNA-3C and the host transcription factor PU.1, ATF4, and IRF7. Since the transcriptional activity of PU.1, ATF4, and IRF7 is repressed early after infection, it is possible that these or other trans-acting factors are not present to transcriptionally activate LMP1 to high levels early after infection. To address the change in LMP1 mRNA stability, published work has demonstrated that a Myc-induced miRNA, miR17, has a negative effect on LMP1 expression in EBV-infected lymphoblastoid cell lines. Furthermore, miR17 is expressed at higher levels early after infection when LMP1 is expressed poorly. To investigate these hypotheses I propose to study the transformation of B cells by EBV in the absence of negative regulation by miR17 as well as further characterize the promoter activity of LMP1 early after infection. The goal of this project is to characterize how EBV dynamically controls the expression of its own transcripts using host factors and how temporal regulation of LMP1 effects B cell transformation.